Abstract
NMR based screening has become an important tool in the pharmaceutical industry. Methods that provide information on the location of small molecule binding sites on the surface of a drug target (e. g. SARby- NMR and related techniques) are of particular interest. In order to extend the applicability of such techniques to drug targets of higher molecular weight, selective labeling strategies may be employed. Dualamino acid selective labeling and site directed non-native amino acid replacement (SNAAR) allow for the selective detection of NMR resonances of a specific amino acid residue. This results in significantly reduced spectral complexity, which not only enables application to higher molecular weight systems, but also eliminates the need for sequential resonance assignment in order to identify the binding site. Regio-selective (or segmental) labeling of an entire protein domain of a multi domain protein may also be achieved. Labeling only a selected part of a multi domain protein (e. g. a catalytic or ligand binding domain) is an attractive way to simplify the spectral interpretation without disturbing the system under study.
Combinatorial Chemistry & High Throughput Screening
Title: Site-Selective Labeling Strategies for Screening by NMR
Volume: 5 Issue: 8
Author(s): Johan Weigelt, Mats Wikstrom, Johan Schultz and Maria J. P. van Dongen
Affiliation:
Abstract: NMR based screening has become an important tool in the pharmaceutical industry. Methods that provide information on the location of small molecule binding sites on the surface of a drug target (e. g. SARby- NMR and related techniques) are of particular interest. In order to extend the applicability of such techniques to drug targets of higher molecular weight, selective labeling strategies may be employed. Dualamino acid selective labeling and site directed non-native amino acid replacement (SNAAR) allow for the selective detection of NMR resonances of a specific amino acid residue. This results in significantly reduced spectral complexity, which not only enables application to higher molecular weight systems, but also eliminates the need for sequential resonance assignment in order to identify the binding site. Regio-selective (or segmental) labeling of an entire protein domain of a multi domain protein may also be achieved. Labeling only a selected part of a multi domain protein (e. g. a catalytic or ligand binding domain) is an attractive way to simplify the spectral interpretation without disturbing the system under study.
Export Options
About this article
Cite this article as:
Johan Weigelt , Mats Wikstrom , Johan Schultz and Maria J. P. van Dongen , Site-Selective Labeling Strategies for Screening by NMR, Combinatorial Chemistry & High Throughput Screening 2002; 5 (8) . https://dx.doi.org/10.2174/1386207023329978
DOI https://dx.doi.org/10.2174/1386207023329978 |
Print ISSN 1386-2073 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5402 |
Call for Papers in Thematic Issues
Artificial Intelligence Methods for Biomedical, Biochemical and Bioinformatics Problems
Recently, a large number of technologies based on artificial intelligence have been developed and applied to solve a diverse range of problems in the areas of biomedical, biochemical and bioinformatics problems. By utilizing powerful computing resources and massive amounts of data, methods based on artificial intelligence can significantly improve the ...read more
Eco-friendly Agents for Biological Control of Pathogenic Diseases
The discovery of an alternative biological approach to disease management includes work on medicinal products derived from natural sources as a starting point for the development of eco-friendly agents for these diseases and the injuries they cause, as well as reducing human contact with hazardous chemicals and their residues. We ...read more
Emerging trends in diseases mechanisms, noble drug targets and therapeutic strategies: focus on immunological and inflammatory disorders
Recently infectious and inflammatory diseases have been a key concern worldwide due to tremendous morbidity and mortality world Wide. Recent, nCOVID-9 pandemic is a good example for the emerging infectious disease outbreak. The world is facing many emerging and re-emerging diseases out breaks at present however, there is huge lack ...read more
Exploring Spectral Graph Theory in Combinatorial Chemistry
Scope of the Thematic Issue: Combinatorial chemistry involves the synthesis and analysis of a large number of diverse compounds simultaneously. Traditional methods rely on brute force experimentation, which can be time-consuming and resource-intensive. Spectral Graph Theory, a branch of mathematics dealing with the properties of graphs in relation to the ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
Related Articles
-
AMPA Glutamate Receptors and Neuropathic Pain
Mini-Reviews in Medicinal Chemistry A Systematic Review and Meta-Analysis of the Safety of Hydroxychloroquine in a Randomized Controlled Trial and Observational Studies
Current Reviews in Clinical and Experimental Pharmacology Anti-Viral
Current Bioactive Compounds Periostin as a Heterofunctional Regulator of Cardiac Development and Disease
Current Genomics Experimental Strategies in Autoimmunity: Antagonists of Cytokines and their Receptors, Nanocarriers, Inhibitors of Immunoproteasome, Leukocyte Migration and Protein Kinases
Current Pharmaceutical Design Preface
Current Drug Metabolism Contactless Core-temperature Monitoring by Infrared Thermal Sensor using Mean Absolute Error Analysis
Recent Patents on Engineering Application of Ligand SAR, Receptor Modeling and Receptor Mutagenesis to the Discovery and Development of a New class of 5-HT2A Ligands
Current Topics in Medicinal Chemistry New Trends of Deep Learning in Clinical Cardiology
Current Bioinformatics Graphical Abstracts
Letters in Drug Design & Discovery Mini-Review on SARS-CoV-2 Infection and Neurological Manifestations: A Perspective
CNS & Neurological Disorders - Drug Targets Nucleotide Binding Affects Intrinsic Dynamics and Structural Communication in Ras GTPases
Current Pharmaceutical Design Machine Learning and Tubercular Drug Target Recognition
Current Pharmaceutical Design "Old Friends in New Guise": Exploiting Privileged Structures for Scaffold Re-Evolution/Refining
Combinatorial Chemistry & High Throughput Screening Meet Our Editorial Board Member
Current Drug Targets Development of Specific Radiopharmaceuticals for Infection Imaging by Targeting Infectious Micro-organisms
Current Pharmaceutical Design SUBJECT INDEX TO VOLUME 1
Current Medicinal Chemistry - Anti-Cancer Agents Microwave Assisted Synthesis: A New Technology in Drug Discovery
Mini-Reviews in Medicinal Chemistry Hernia Surgical Treatment; Multi-options and Paucity of Statistical Conformation for the Preferred Surgical Option
New Emirates Medical Journal The Role of Amino Acids in the Modulation of Cardiac Metabolism During Ischemia and Heart Failure
Current Pharmaceutical Design